Abstract

BackgroundRupture of the fetal membranes is a common harbinger of imminent labor and delivery. Telomere shortening is a surrogate for oxidative stress (OS) and senescence. Fetal leukocyte and placental membrane DNA telomere lengths were evaluated to determine their association with preterm prelabor rupture of the membranes (pPROM) or spontaneous preterm births with intact membranes (PTB), compared to term birth.MethodsTelomere lengths were quantified in cord blood leukocytes (n = 133) from three major groups: 1) pPROM (n = 28), 2) PTB (n = 69) and 3) uncomplicated full term births (controls, n = 35), using real-time quantitative PCR. Placental membrane specimens (n = 18) were used to correlate fetal leukocyte and placental telomere lengths. Telomere length differences among the groups were analyzed by ANOVA. Pearson correlation coefficients determined relationships between leukocyte and placental membrane telomere lengths.ResultsIn pregnancies with intact membranes, fetal leukocyte telomere length was inversely proportional to gestational age. The mean telomere length decreased as gestation progressed, with the shortest at term. pPROM had telomere lengths (9962±3124 bp) that were significantly shorter than gestational age-matched PTB (11546±4348 bp, p = 0.04), but comparable to term births (9011±2497 bp, p = 0.31). Secondary analyses revealed no effects of race (African American vs. Caucasian) or intraamniotic infection on telomere length. A strong Pearson's correlation was noted between fetal leukocyte and placental membrane telomere lengths (ρ = 0.77; p<0.01).ConclusionsFetal leukocyte telomere length is reduced in pPROM compared to PTB but is similar to term births. pPROM represents a placental membrane disease likely mediated by OS-induced senescence.

Highlights

  • Preterm (,37 weeks of completed gestation) prelabor rupture of the membranes occurs in about 3–4% of all pregnancies. pPROM is directly antecedent to 40% to 50% of all preterm births and occurs in many women without identifiable risk factors [1]

  • While several tests are available to confirm pPROM post facto, no method exists to reliably predict pPROM [3,4]. This dilemma is mostly attributable to the fact that precise risk factors, causes, or pathways resulting in pPROM are unknown

  • Racial disparity is associated with pPROM and preterm birth rates and we have provided evidence that genetic and inflammatory markers may contribute to this phenomenon [19]

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Summary

Introduction

Preterm (,37 weeks of completed gestation) prelabor rupture of the membranes (pPROM) occurs in about 3–4% of all pregnancies. pPROM is directly antecedent to 40% to 50% of all preterm births and occurs in many women without identifiable risk factors [1]. Preterm (,37 weeks of completed gestation) prelabor rupture of the membranes (pPROM) occurs in about 3–4% of all pregnancies. While several tests are available to confirm pPROM post facto (e.g. amniotic fluid pooling, ‘‘ferning’’, nitrazine reaction, and AmnisureH), no method exists to reliably predict pPROM [3,4]. This dilemma is mostly attributable to the fact that precise risk factors, causes, or pathways resulting in pPROM are unknown. Fetal leukocyte and placental membrane DNA telomere lengths were evaluated to determine their association with preterm prelabor rupture of the membranes (pPROM) or spontaneous preterm births with intact membranes (PTB), compared to term birth

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